The overall goal of this SPORE in lung cancer proposal is to translate recent advances in the understanding of the molecular pathogenesis of lung cancer into new methods to prevent, diagnose, and treat lung cancer. This SPORE is a logical development of the planning P20 SPORE in Lung Cancer awarded 3 years ago to UTSW. It developed out of 32 years of planning effort between UT Southwestern Medical Center (UTSW) and M.D. Anderson Cancer Center (MDACC), bringing together two major complementary strengths in lung cancer research in the areas of prevention, molecular pathogenesis, early detection, and development of novel therapies based on translational research. This SPORE consists of 5 inter-related projects and 3 supporting Cores. The projects in Lung Cancer are: 1. Identification of 3p Recessive Oncogenes; 2. Genetic Susceptibility: 3. Molecular Early Detection; 4. Chemoprevention in Former Smoker; 5. Mutant p53 Epitope Targeting. The Cores are: A. Administrative; B. Pathology and Tissue Resource; and C. Informatics. All of the scientific projects are: a) translational in nature; b) focus on human lung cancer; c) arose out of conjoint planning between UTSW and MDACC and involve investigators from both institutions as Co- investigators; d) interact with other projects; e) include basic and clinical investigators; and f) utilize Core resources. There is a substantial plan for innovative Developmental Projects, and a plan for Career Development that has already been productive from the UTSW P20 planning SPORE effort. There is a heavy emphasis on prevention, early detection and the development of novel therapies that could be applied to very early stage disease. In addition, the Developmental Program includes a project for the testing for genetic predisposition to nicotine dependency as a new approach to identifying persons at high risk of developing lung cancer. Achievement of the aims and objectives of this proposal will result in a major decrease in the incidence, morbidity and mortality of lung cancer.